Effect of an angiotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril.

Abstract

The role of angiotensin II and kinins on the renal cortical and papillary hemodynamic and on the sodium and water excretory responses to converting enzyme inhibition with captopril was examined in euvolemic Munich-Wistar rats. Cortical and papillary blood flows were measured using a laser Doppler flowmeter. Cortical blood flow increased 28% after blockade of angiotensin II receptors with DuP 753 (2 mg/kg i.v., n=6). Captopril (2 mg/kg i.v., n=6) had no effect on cortical blood flow in rats pretreated with the angiotensin II antagonist DuP 753 had no effect on papillary blood flow, nor did it prevent the rise in papillary blood flow produced by captopril (2 mg/kg, n=6). Infusion of a kinin receptor antagonist, r>Arg,[Hyp 3 ,Thi M , D-Phe 7 ]-bradykinin (2.5 /tg/min i.v.), reduced basal papillary blood flow by 15% and blocked the rise in papillary blood flow produced by captopril. Renal blood flow rose by 11% after DuP 753 (2 mg/kg, n=6), and subsequent administration of captopril and the kinin antagonist had no effect on renal blood flow. Urine flow and sodium excretion increased after DuP 753, but captopril produced additional increases in urine flow and sodium excretion of 68% and 46%, respectively. Fractional sodium excretion rose from 0.85±0.15% to 1.56±0.14% after captopril. Infusion of the kinin antagonist returned sodium and water excretion to control levels, but fractional sodium excretion was not significantly altered.' Giomenilar filtration rate was not altered by DuP 753 or captopril; however, it fell from 1.6±0.1 to 1.2±0.1 ml/min/g kidney wt during infusion of the kinin antagonist This fall in giomenilar filtration rate was associated with a 30% fall in the ultrafiltration coefficient These results indicate that captopril alters renal hemodynamics through mechanisms other than blockade of the renin-angiotensin system. In particular, its effects on papillary blood flow and giomenilar dynamics may be due to alterations in the intrarenal levels of kinins. (Hypertension 1991;17:1038-1044) C onverting enzyme inhibitors (CEIs) are antihypertensive agents that promote sodium excretion at lower levels of arterial pressure. However, the mechanisms underlying the natriuretic and antihypertensive actions of CEIs remain uncertain. It generally is thought that these drugs act by blocking the renin-angiotensin system in the kidney and the peripheral vasculature. However, CEIs lower arterial pressure in nephrectomized animals, as well as in rats pretreated with angiotensin (Ang) II antagonists.

Role of renal NO production in the regulation of medullary blood flow

“…We have observed that rats pretreated with a cyclooxygenase inhibitor (meclofenemate) exhibited a significant reduction of medullary flow with subpressor intravenous infusion of ANG II (61). Similar responses have been observed with kinin receptor antagonists (24,99). It has now also been found that the hemoxygenase enzymes are present at significantly greater concentrations in the renal medulla than in the cortex, and the production of medullary CO via the hemoxygenase pathway may participate in the control of flow to this region (134).…”

Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides.

“…33 -3841 For most of these studies, however, the very high levels reported for circulating immunoreactive kinins raise questions concerning the validity of their estimation. 12 Indirect evidence for a role of BK-(1-9) in mediating some of the effects of ACE inhibitors has come from the use of BK-(l-9) antagonists, kinin antibodies, and aprotinin, which partially reverse the hypotensive effect of ACE inhibitors 79 -42 - 48 and also partially reverse the effects of ACE inhibitors on renal papillary blood flow, urine flow, and sodium excretion 49 -50 on cardiac hypertrophy 11 and on neointima formation. 13 In the present study perindopril administration increased BK-(l-9) levels in blood and tissues.…”

Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation

“…Nevertheless, ACE inhibitors also favor the accumulation of kinins by preventing their degradation (10). In addition, compelling evidence suggests the involvement of kinins in the renal effects of ACE inhibitors (22,39), and Tschöpe et al (48) have shown that kidney B 2 R is upregulated in streptozotocin (STZ)-diabetic rats. Nevertheless, the roles of BK and B 2 R in the protective effects of ACE inhibitors during the development of DN remain to be established.…”